A recent study undertaken by investigators at five research centres, amongst which is the CSIC-University of the Basque Country Biophysics Unit, provides new clues for the understanding of the 'cell suicide' process.
The research was published in the latest issue of the journal Cell.
Our bodies daily eliminate in a controlled manner more than 100 million defective cells, by means of a procedure known as 'cell suicide' or apoptosis. This is a highly complicated process, any imbalances thus arising causing serious diseases, prominent amongst which is cancer. Over the past two decades it has been possible to identify various cellular components involved in apoptosis. Nevertheless, there are still important unresolved questions about the functioning of certain key elements in this great cell riddle.
This study has revealed that three essential components of the apoptotic process, the BAX and DRP-1 proteins and cardiolipin, act in a joint manner to produce a large hole in the external membrane of the mitochondria, proving to be lethal for the cell.
But probably the most surprising aspect of the research is that the researchers have managed to decipher a new 'language' used by BAX and DRP-1 for communicating: these two proteins do not interact with each other physically, as usually happens, but they do so through the lipids of the membrane.
"More specifically, what one of the proteins (DRP-1) does is to deform the lipid bilayer of the membrane and the resulting structure is what apparently enables the activation of the second protein (BAX)," explained Mr Gorka Basañez, from the CSIC-UPV/EHU Biophysics Unit, and one of the authors of the research. These findings can open new ways to the rational development of anti-tumour pharmaceutical drugs, specifically targeting these components of the apoptotic cell machinery.
Taking part in this research, led by Professor Jean-Claude Martinou of the Department of Cell Biology at the University of Geneva (Switzerland), were, apart from the CSIC-UPV/EHU Biophysics Unit, the universities of Salzburg (Germany), Hanover (Germany) and Florida (USA).
- Sylvie Montessuit, Syam Prakash Somasekharan, Oihana Terrones, Safa Lucken-Ardjomande, Sébastien Herzig, Robert Schwarzenbacher, Dietmar J. Manstein, Ella Bossy-Wetzel, Gorka Basañez, Paolo Meda, Jean-Claude Martinou. Membrane Remodeling Induced by the Dynamin-Related Protein Drp1 Stimulates Bax Oligomerization. Cell, 2010; 142 (6): 889-901 DOI: 10.1016/j.cell.2010.08.017
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